Most cancers are currently incurable, partly due to abnormal post-translational modifications (PTMs). In this study, we initially used multiple myeloma (MM) as a working model and found that SUMOylation activating enzyme subunit 1 (SAE1) promotes the malignancy of MM. Through proteome microarray analysis, SAE1 was identified as a potential target for bioactive colcemid or its derivative colchicine. Elevated levels of SAE1 were associated with poor clinical survival and increased MM proliferation in vitro and in vivo. Additionally, SAE1 directly SUMOylated and upregulated the total protein expression of p27, leading to LLPS-mediated nuclear export of p27. Our study also demonstrated the involvement of SAE1 in other types of cancer cells, and provided the first monomer crystal structure of SAE1 and its key binding model with colchicine. Colchicine also showed promising results in the Patient-Derived Tumor Xenograft (PDX) model. Furthermore, a controlled clinical trial with 56 MM patients demonstrated the clinical efficacy of colchicine. Our findings reveal a novel mechanism by which tumor cells evade p27-induced cellular growth arrest through p27 SUMOylation-mediated nuclear export. SAE1 may serve as a promising therapeutic target, and colchicine may be a potential treatment option for multiple types of cancer in clinical settings.

OBJECTIVE: To investigate the clinical characteristics and related risk factors of Clostridium difficile infection (CDI) in intensive care unit (ICU). METHODS: A retrospective study was conducted. Patients with diarrhea admitted to the ICU of the General Hospital of Ningxia Medical University from May 1 to August 30, 2023 were selected. Patients were divided into CDI group and non-CDI group based on the presence or absence of CDI. Clinical data from two groups of patients meeting the criteria were collected and compared, including gender, age, acute physiology and chronic health evaluation II (APACHE II), length of hospital stay, serum lactic acid, parenteral nutrition time, white blood cell count (WBC), procalcitonin (PCT), C-reactive protein (CRP), coagulation indicators, albumin, antibiotic exposure, etc. Multivariate Logistic regression analysis was performed to analyze the risk factors for CDI in ICU diarrhea patients. Receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of each index for CDI in diarrhea patients. RESULTS: A total of 24 patients with diarrhea were enrolled, including 9 patients in the CDI group and 15 patients in the non-CDI group. The time of parenteral nutrition in the CDI group was significantly longer than that in the non-CDI group [days: 18.0 (13.5, 19.5) vs. 10.0 (4.0, 18.0)], the serum lactic acid level [mmol/L: 4.40 (3.00, 15.25) vs. 2.50 (1.90, 3.20)] and the ratio of serum lactic acid > 3.9 mmol/L [66.67% (6/9) vs. 6.67% (1/15)] were significantly higher than those in the non-CDI group, with statistical significance (all P < 0.05). Multivariate binary Logistic regression analysis showed that the serum lactic acid level of the patients was an independent risk factor for CDI [odds ratio (OR) = 3.193, 95% confidence interval (95%CI) was 1.011-10.080, P = 0.048]. ROC curve showed that serum lactic acid level had a high predictive value for CDI in ICU patients with diarrhea, and the area under the curve (AUC) was 0.815, respectively. When the cut-off value of serum lactic acid was 3.9 mmol/L, the sensitivity was 66.7% and the specificity was 93.3%. CONCLUSION Patients with diarrhea who have higher serum lactate levels (> 3.9 mmol/L) on admission are at increased risk of developing CDI.
Humans ; Retrospective Studies ; Risk Factors ; Intensive Care Units ; Clostridium Infections ; Clostridioides difficile ; Male ; Female ; Middle Aged ; Aged ; Diarrhea/microbiology* ; Logistic Models ; ROC Curve ; Adult

"Let food be thy medicine and medicine be thy food"-the ancient adage proposed by Greek philosopher Hippocrates of Kos thousands of years ago already acknowledged the importance of the beneficial and health-promoting effects of food nutrients on the body (Mafra et al., 2021). Recent epidemiological and large-scale community studies have also reported that unhealthy diets or eating habits may contribute heavily to the burden of chronic, non-communicable diseases, such as obesity, type 2 diabetes mellitus (T2DM), hypertension, cardiovascular disease (CVD), cancer, neurodegenerative diseases, arthritis, chronic kidney disease (CKD), and chronic obstructive pulmonary disease (COPD) (Jayedi et al., 2020; Gao et al., 2022). Emerging evidence highlights that a diet rich in fruits and vegetables can prevent various chronic diseases (Chen et al., 2022). Food bioactive compounds including vitamins, phytochemicals, and dietary fibers are responsible for these nutraceutical benefits (Boeing et al., 2012). Recently, phytochemicals such as polyphenols, phytosterols, and carotenoids have gained increasing attention due to their potential health benefits to alleviate chronic diseases (van Breda and de Kok, 2018). Understanding the role of phytochemicals in health promotion and preventing chronic diseases can inform dietary recommendations and the development of functional foods. Therefore, it is crucial to investigate the health benefits of phytochemicals derived from commonly consumed foods for the prevention and management of chronic diseases.
Humans ; Diabetes Mellitus, Type 2 ; Diet ; Vegetables/chemistry* ; Cardiovascular Diseases/prevention & control* ; Phytochemicals ; Chronic Disease

Objective:To explore the correlation between the single nucleotide variation of profibrin-1 (PFN1) gene and secondary osteoporosis (OP) after stroke and its influence on bone metabolism indexes.Methods:120 patients with post-stroke hemiplegia who were treated in our hospital from Jan. 2019 to Jun. 2023 were selected as study objects and divided into OP group and non-OP group. Levels of vitamin D[25- (OH) D], tartrate-resistant acid phosphatase (TRAP) , osteocalcin (BGP) , serum type I procollagen amino terminal prolongation brain (P1NP) and type I collagen basal terminal β special sequence (β-CTX) were detected in all patients. Two SNPS (rs6559 and rs78224458) in PFN1 gene were genotyped.Results:There were significant differences in serum 25- (OH) D, TRAP, P1NP and β-CTX levels between OP group and non-OP group ( P<0.05) . The GG, GA and AA genotypes at rs6559 of PFN1 gene were significantly different between OP and non-OP patients ( P<0.05) . The combined model showed that compared with GG genotype carriers, the risk of secondary OP in GA and AA genotype carriers was 3.250 and 5.417 times higher, respectively. The results of the dominant model showed that the risk of secondary OP was 3.792 times higher in patients with mutant genes (GA or AA) than in patients with GG genotype. Recessive model results showed that patients with AA genotype had a 3.810-fold increased risk of secondary OP compared with GG and GA carriers. There was no significant difference in TT, TC, CC genotype distribution, genetic model and allele frequency at rs78224458 of PFN1 gene between OP patients and non-OP patients ( P>0.05) . There were no significant differences in 25- (OH) D, TRAP or BGP among the rs6559 GG, GA and AA genotypes of PFN1 gene ( P>0.05) , while there were significant differences in P1NP andβ-CTX levels among the three groups ( P<0.05) . Conclusion:The rs78224458 variation of PFN1 gene is associated with secondary OP in patients with hemiplegia after stroke, and may affect the bone metabolism indexes of patients.

The level of serum fibroblast growth factor-21 (FGF-21) in patients with type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease (NAFLD) was determined by ELISA.The results showed that serum FGF-21 level in these patients was higher than that in type 2 diabetic patients [(266.55 ± 21.24 vs 220.32 ± 22.68) ng/L,P＜ 0.01].Serum FGF-21 levels in both groups were significantly higher than that in normal control group [(173.52 ± 16.18) ng/L,P＜0.01].Serum FGF-21 level was positively correlated with waist circumference,blood glucose,and triglyceride.FGF-21 may contribute to the development of NAFLD in the patients with type 2 diabetes mellitus.

Aged ; Humans ; Kidney Neoplasms ; pathology ; Male ; Neoplasm Metastasis ; Paranasal Sinus Neoplasms ; secondary